A wholly novel approach to the synthesis of optically pure natural prostaglandins and analogs thereof is proposed. Based upon the ready availability by fermentation of the mold metabolite, terrein, a flexible synthetic process has been partially completed which will make these compounds available for pharmacological evaluation and clinical use. Optically active terrein is available in large quantity by fermentation of Aspergillus terreus and flavus on inexpensive media and contains a cyclopentenone moiety which has correct functionality and absolute configuration for chemical transformation to a wide variety of prostaglandins potentially or presently useful for a wide variety of medicinal uses such as the control of fertility, interruption of pregnancy, treatment of hypertension, ulcers, and possible asthma. Dissociation of these various activities for practical therapeutic application requires introduction of the appropriate chemical features into the prostanoid skeleton. This requires a versatile synthetic approach from readily available starting materials. This grant details major chemical approaches to prostaglandins from such a starting material and each has been carried out far enough to suggest that they will successfully solve the problem posed. These methods, and other derived from them, will also inexpensive preparation of all the known prostaglandins and most of the synthetic analogs presently described and do not require a resolution step. The compounds which are produced which are new to the literature will be evaluated in vivo in experimental animals for their pharmacologic profile. Some of the novel target compounds are designed to have relatively long tissue half-lives because they carry structural features which will suppress metabolic inactivation.